Non-steroidal anti-inflammatory drugs (NSAIDS): good for me or bad for me?

Non-steroidal anti-inflammatory drugs (NSAIDS) are a mainstay of arthritis treatment. However, recent concerns regarding their cardiovascular safety make their routine use in arthritis therapy problematic.

The primary toxicity associated with NSAIDS is gastrointestinal with the potential for ulcer formation and bleeding. While COX-2 selective drugs like Celebrex reduce the risk, they do not do away with the risk entirely. In addition, if patients are on concomitant aspirin treatment for stroke or heart attack prophylaxis, the risk for gastrointestinal events becomes the same for patients on selective COX-2 drugs versus plain NSAIDS. In addition, there have been reports of small intestinal ulceration as well as colonic ulceration as well with these medications. There is some evidence that simultaneous treatment with proton pump inhibitors may help protect the stomach.

There is no question that NSAIDS elevate the risk for cardiovascular events such as heart attacks and strokes. The exact incidence tends to vary somewhat with different anti-inflammatory drugs. The worst offender, rofecoxib (Vioxx), was removed from the market by the FDA several years ago. All other NSAIDS have approximately the same risk. They should be used cautiously, if at all, in patients with prior cardiac problems.

NSAIDs also possess a certain risk for kidney toxicity which contributes to fluid retention and edema while also promoting the aggravation of hypertension. However, often underappreciated are the blood pressure and kidney effects of NSAIDs. It has long been noted that a potential risk of NSAIDs is a destabilization of blood pressure control in hypertensive patients, particularly if they are treated with ACE inhibitors. Direct kidney toxicity, deleterious changes in kidney blood flow, and decline in kidney function are seen as a consequence in patients treated with NSAIDs. Edema (fluid retention) and worsening of congestive heart failure (CHF) are also potential known consequences of NSAIDs. NSAIDs also interfere with the cardioprotective effects of aspirin.

However… all is not doom and gloom for NSAIDS.

A study of Medicare patients with osteoarthritis provides additional evidence that non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin reduce the risk of colorectal cancer. Earlier investigations of the drugs’ impact on tumor development could not rule out the possibility that an observed protective effect was caused by other preventive health care measures. Researchers note, however, that safer drugs are probably needed before regular preventive therapy can be recommended.

Elizabeth Lamont, MD, MS, of the Massachusetts General Hospital Cancer Center, the study’s lead author, states, “Although patients face risks such as bleeding or kidney damage from NSAIDS, they probably are at a lower risk of developing colorectal cancer.” Because of the risks posed by the dosage used to treat osteoarthritis, she stresses that currently available NSAIDs should not be used solely to prevent cancer.

Earlier randomized trials indicated that NSAID treatment could possibly prevent the development of precancerous colorectal polyps, but whether or not such therapy also reduces the risk of invasive colorectal cancer has not yet been confirmed. Those trials used relatively low doses of aspirin and showed no significant differences in colorectal cancer rates between the aspirin and placebo groups. While many observational studies have shown a protective effect of NSAIDs against colorectal cancer, interpretation of some of those results may have been clouded by other healthy behaviors of the participants.

First, the researchers reviewed data from the 1993-94 National Ambulatory Medical Care Survey, in which physicians report on the diagnoses of and treatments prescribed to patients seen during a randomly selected week. Those results verified that older patients with osteoarthritis were more than four times as likely to take NSAIDs as were those without osteoarthritis. They then analyzed information from the Survival Epidemiology and End-Results (SEER)-Medicare program, studying groups of elderly Medicare patients with and without colorectal cancer, to search for associations with NSAID use.

Comparing information on 4,600 individuals with colorectal cancer to data from 100,000 controls, they found that a history of osteoarthritis was associated with a 15 percent reduction in the likelihood of a colorectal cancer diagnosis.

“The magnitude of colorectal cancer risk reduction between patients with and without osteoarthritis is completely consistent with the risk reduction for pre-cancerous polyps reported in clinical trials of NSAIDs,” Lamont says.

The study appears in the August 2007 Journal of General Internal Medicine.

The study also raises the 64 dollar question which is “What is the risk/benefit of taking an NSAID for cancer prevention versus the risk of cardiovascular side-effects?

As a practicing rheumatologist, I am in a constant battle with cardiologists who want to stop NSAID therapy. In addition to quality of life issues, this most recent study also raises another issue- that of possible colon cancer prevention.

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